ABSTRACT While survival after sudden cardiac arrest (CA) has improved with modern resuscitation efforts, survivors can exhibit multiple motor and cognitive impairments due to the neurological sequelae resulting from the associated hypoxic-ischemic brain injury (HIBI). Further, these survivors represent a ?new? population for rehabilitationists to treat who have these impairments. Current practice is to borrow management strategies used with other acquired brain injury populations to manage issues like low cognitive arousal, agitation/restlessness, depression/anxiety, and movement disorders (myoclonus). However, the pathology underlying these seemingly overlapping symptoms may be very different depending on the etiology of the brain injury. Our pilot data using fast scan cyclic voltammetry (FSCV), a method to conduct in vivo, real-time characterization of presynaptic DA transmission in a model of mild ventricular fibrillation cardiac arrest (VF-CA). Our data show that by 2 weeks after VF-CA, there are substantial increases in maximal striatal evoked DA overflow, and there is increased DA transporter (DAT) expression to partially compensate for dysregulated increases in evoked DA overflow. Increased evoked striatal DA overflow can be further augmented with increasing severity of the VF-CA insult. Together, the data suggest DA transmission derangements after experimental VF-CA are very different than what is observed with similar studies done in our laboratory with experimental traumatic brain injury (TBI), where there are significant DA transmission deficits and also compensatory striatal DAT expression reductions. We also show that we can elicit myoclonus behavior in this VF-CA model and that striatal neuroinflammation (e.g. high TNF?) is a prominent feature of VF-CA, which may impact both striatal DA transmission and behavior after CA. We also show that asphyxial CA (ACA) yields more neurological injury when compared with a similar VF- CA insult and unique neuroinflammation patterns. Together, the data suggest a need for different clinical treatment strategies used to treat the CA population clinically than what is used to treat TBI. Thus our goal is to develop multiple CA models of survival that can be used as a test bed for examining rehabilitation focused treatments that impact inflammation, DA neurotransmission and associated behavioral deficits. We hypothesize 1) striatal damage and inflammation associated with HIBI results in dysregulated increases in presynaptic DA transmission profiles over time that are sensitive to CA model type (VF-CA vs. ACA) and insult severity 2) altered DA transmission and striatal damage associated with HIBI is associated with myoclonus, cognitive deficits, and maladaptive behaviors. Our goal is use this model to understand mechanisms underlying observed changes in DA neurotransmission and responsiveness to dopamine modulation and reduction agents. This translational research collaboration is a novel extension of our excellence in CA clinical care program. The proposed work marks a paradigm shift in how we rehabilitate those surviving CA as we begin a research pipeline that identifies tailored and effective treatments for rehabilitation and recovery for the population surviving CA.